From Shakespeare to Schizophrenia

By Courtney Reyers, NAMI Publications Manager

“It’s important to know how much people living with mental illness pervade our society and do great things. People with mental illness enrich our lives.”

This year, NAMI honored Dr. Nancy C. Andreasen with its 2012 Scientific Research Award, which recognizes outstanding individuals who have made significant contributions to the understanding of mental illness and the advancement of treatment for the people who live with these illnesses.

A foremost authority on schizophrenia and a recipient of the President's National Medal of Science, Dr. Andreasen pioneered the use of magnetic resonance imaging (MRI) to identify brain mechanisms of mental illness. She was also among the first to pioneer the integration of neuroimaging and genomics. Much of her current work focuses on genetic/genomic regulation of illness onset, course and outcome, particularly with respect to neuroimaging brain measures.

Dr. Andreasen's research has also provided insight into brain mechanisms underlying language, emotion and the creative process. She led the first extensive empirical study of creativity and was the first to recognize the association between creativity and bipolar disorder. She is currently conducting a second study of creativity in prominent artists and scientists.

Her contributions to science and to educating the lay public have been enhanced by her unusual combination of expertise in literature—her Ph.D. is in Renaissance English Literature—and science. Her work was among the first to suggest that schizophrenia is linked to abnormal brain development and that a decrease in the size of the brain's frontal lobe is associated with certain symptoms of the disorder, including impaired cognitive function. She has used her literary skills to write books designed to educate the lay public and to reduce stigma. Among her 15 books is a "brain trilogy" written to educate nonscientists about neuroscience, mental illness and creativity: The Broken Brain, Brave New Brain and The Creating Brain.

NAMI spoke with Dr. Andreasen to find out more about her life, her work and her passion.

NAMI: What is neuroimaging? Can you tell us about your work with MRI?

Andreasen: Neuroimaging is a broad term for MRI, positron emission tomography (PET) scanning—any kind of scanning technique you use to study the brain. MR imaging is not invasive and is widely used today. It’s a no-risk procedure, is easy to do and you can generate images of brain anatomy [the black and white images] and brain function [colored images]. There are numerous subfields in neuroimaging. People are looking at cognitive functions ranging from attention to language to memory to motor coordination to stress response—you have endless questions you can examine.

I was part of a team that conducted the first study in brain abnormalities in 1986, which rolled into a landslide of studies to use MR to measure brain structure in a lot of illnesses, including autism. Being the first, you realize that you do an imperfect study and you want to continue the work. Very early on, we recognized that software development to automate measurements to make the data valid was key, so we also put a huge amount of effort into software development—now we can generate measurements within 15 minutes or less.

Over the years, doctors and researchers began to develop more elegant designs and paradigms to study different kinds of brain functions. In the early days, researchers focused on hard cognitive science, asking questions like “how do people learn a basic function, like how to recognize a face?” Today we’re looking at more complex things, like how people experience emotions. Or what happens in the brain when someone experiences pleasure and how is that different from asking that person to describe how pleasurable something is?

[At the University of Iowa], we had someone from our sociology department who was using MR to look at stereotypes of social class and race. You can call it “neurosociology.” Economists are interested in how people make financial decisions—whether they are willing to take a small reward early or delay and take a greater reward later. What started as a small field limited to a few people has expanded to people in the arts and science, businesses, sociology, religious studies. Even the military—they want to understand the effects of stress. It pervades every aspect of things that the human mind does. Bottom line, it’s become useful in studying both normal brain structure and function as well as illness.

NAMI: Your work around creativity and bipolar is fascinating—I have seen a link between mental illness and creative people in my work as a journalist interviewing musicians, actors and writers. I often ask them about this link and they say that they see it a lot of mental illness in their line of work. What can you tell us about that connection?

Andreasen: In a way, this is another first in my career. My first Ph.D. was in Renaissance English literature, and I taught for five years before I went on to med school (and three of those years were here at the University of Iowa Writer’s Workshop). I decided to do a study of creativity in writers in the workshop as a side project. My hypothesis was that the writers wouldn’t have mental illness, but that I would find it in their family members. I had done a lot of work on James Joyce, who had a daughter with schizophrenia, and Albert Einstein, who had a son with schizophrenia—there were a lot of examples of the link between creativity and mental illness.

As I began to contact the workshop writers, frankly I was astounded when they came in, one after the other, and told me about their own problems with mood disorders—to the tune of 80 percent of the writers I interviewed. It was one of those instances where you’re taught that science provides hypotheses and then you confirm them, but it’s far more interesting when you can’t confirm them. These writers had a high rate of mood disorders as well as a high level of creativity in their families. Since then other researchers have done studies with slightly different designs, and it’s been a fairly well-replicated finding.

It’s difficult though because you have to identify creativity and identify a group. I’m currently replicating my first study in a second study. I said to myself: Did I get these results because I studied writers? Is there something about being a novel writer that requires a lot of introspection and self-criticism? What would happen if I studied other creative types? You mentioned music, acting—and there are the sciences. The multiple examples of schizophrenia I can think of are based in science and math—what would I find if I studied schizophrenia instead of bipolar?

One of the issues is recruiting people who are both prominent and busy. For my second study, I would use people who are already well-recognized, who have won Nobel and Pulitzer prizes, the Fields Medal, math prizes—people like George Lucas who is well-known in his field.

NAMI: So what drives you?

Andreasen: I have a real passion about educating people about mental illness and reducing stigma. I have written three books for lay audiences that I hoped would do those things. They provide access to accurate information to people and their family members that doesn’t oversimplify or talk down to them, and that these are real illnesses and need to be treated w the same respect as other illness. If you want to make me angry, just call someone with mental illness “crazy.” One of the things I’m really upset about these days is that so many resources are being pulled away from the care of people with mental illness, it’s being done everywhere—the government, health care delivery systems, community mental health centers—to save money. In psychological practices, doctors are trying to get patients out in 15 minutes. People with mental illness deserve better than they’re getting. I’m getting set to write another book. Each of the books I’ve written has been triggered by a personal experience with how wrong the public’s experience with mental illness is, or a health care provider’s viewpoint is. In a recent issue of Time Magazine, in the context of these killings of these young men and gun control, an article flippantly said, “the problem is that crazy people have access to guns.” That [Time Magazine] would allow that kind of language usage is upsetting.

The truth is I’ve had one experience—and it’s 100 percent private—but it was not the trigger that gave me the passion I have. The trigger is the patients that I have seen and continue to see. Someone like Kay Jameson, and I myself, I think are pretty darn sane. My husband would say, “God seems to be trying you.” I’ve had a lot of personal tragedy, my first husband died from cancer, my oldest daughter just died from cancer. And, frankly, being a woman coming up through the medical school system in the 1960s and ‘70s because women were truly discriminated against then. My response is not depression, it’s what I call the “O-3 model:” outwork, outsmart and outlive them!

NAMI: What was it like working on the DSM (the Diagnostic and Statistical Manual of Mental Disorders, published by the American Psychological Association (APA)) task force? Did you find it rewarding, frustrating, or both?

Andreasen: I was involved with DSM at two different time points. The first being the DSM-III—that was in the early days when there was a tremendous excitement about making diagnoses more reliable and valid. That particular DSM was generated when psychoanalysis was still the prevailing model in American psychology at that time. Those of us who were developing that DSM generally came from a more biologically-oriented field, and that’s when I wrote The Broken Brain. Most people thought of it in terms of the psychodynamic model and the thesis of Broken Brain was that [how we look at the brain] would change to a biological model. DSM III was exciting, and was done by a small group of people and we worked very well together. I think we did a lot of things right. We were pleased with the outcome at that time. What we didn’t expect was the enormous impact the DSM would have on practices, diagnosis, the insurance industry, the legal profession—and neither did the APA. In fact after it came out, it was chronically out of print.

I agreed to do the DSM-IV and chair the schizophrenia workgroup because the DSM-III said nothing about negative symptoms, and I was one of the first to introduce negative symptoms into psychiatry. I developed the first scales for rating negative symptoms, so I wanted to make sure that negative symptoms got acknowledged in DSM-IV. I’m not involved at all in DSM-5—III and IV were quite enough for me.

[In 2007], I wrote an article, “DSM and the Death of Phenomenology in America: An Example of Unintended Consequences” (Schizophrenia Bulletin). The gist is that those of us who were involved in it had really the best of intentions in terms of helping clinicians and patients by demystifying psychiatry and making the diagnostic process more transparent and reliable. We were surprised that it had unintended consequences, misunderstandings and abuses. These days, I’m pretty critical of the DSM approach to diagnosis. I’ve always thought it very important to treat individuals as a person versus a diagnosis. You have to put everyone into a personal context—family work, personal interests. The DSM doesn’t address that at all. It’s more “use the symptom checklist and you’re done,” and that’s not what psychiatry should be about. The DSM encourages that and it’s become overvalued.

NAMI: What do you hope the future looks like for people with mental illness?

Andreasen: It should be an option for a psychiatrist to order a MR scan whenever he or she thinks it might be informative—such as when somebody has an odd presentation, an odd age for onset, unexpected motor symptoms. Scanning is not yet at the point where it’s diagnostic—although some doctors would claim otherwise. But I’m one of the first pioneers in the field and I’ve been doing it for 30 years and I would know if MR scans were diagnostic—and they’re not. They might provide information, but you cannot take any kind of MR scan and make a diagnosis, with the possible exception of Alzheimer’s disease—there are PET scans approved for the FDA for that.

It’s a matter of time, money and technology development. Can we use FMR to look at brain circuitry disruptions that might lead to psychosis? We haven’t done the study yet, we don’t know what the results will be and if we did, could we link them to genetic measurements as well? If not diagnostic, let’s at least make things predictive. Predication is important as well. If I have a genetic and imaging profile of somebody and combine them, I can predict that this person may be more sensitive to an antipsychotic, then I’ll use medication a instead of medication b. It’s not saying this person has schizophrenia, but it helps to say that this person is sensitive to medical side effects and therefore should have certain treatment.

Dr. Andreasen served as editor-in-chief of The American Journal of Psychiatry for 13 years. She also served on the DSM-III and DSM-IV task forces, developing the first widely used scales for rating the positive and negative symptoms of schizophrenia. Today, she is the director of the Psychiatry Iowa Neuroimaging Consortium at the University of Iowa Carver College of Medicine. Read more about Dr. Andreasen at nancyandreasen.com.